Surgery for Glioblastoma: Impact of the Combined Use of 5-Aminolevulinic Acid and Intraoperative MRI on Extent of Resection and Survival

Abstract

BackgroundThere is rising evidence that in glioblastoma(GBM) surgery an increase of extent of resection(EoR) leads to an increase of patient’s survival. Based on histopathological assessments tumor depiction of Gd-DTPA enhancement and 5-aminolevulinic-acid-fluorescence(5-ALA) might be synergistic for intraoperative resection control.ObjectiveTo assess impact of additional use of 5-ALA in intraoperative MRI(iMRI) assisted surgery of GBMs on extent of resection(EoR), progression free survival(PFS) and overall survival(OS).MethodsWe prospectively enrolled 33 patients with GBMs eligible for gross-total-resection(GTR) and performed a combined approach using 5-ALA and iMRI. As a control group, we performed a retrospective matched pair assessment, based on 144 patients with iMRI-assisted surgery. Matching criteria were, MGMT promotor methylation, recurrent surgery, eloquent location, tumor size and age. Only patients with an intended GTR and primary GBMs were included. We calculated Kaplan Mayer estimates to compare OS and PFS using the Log-Rank-Test. We used the T-test to compare volumetric results of EoR and the Chi-Square-Test to compare new permanent neurological deficits(nPND) and general complications between the two groups.ResultsMedian follow up was 31 months. No significant differences between both groups were found concerning the matching criteria. GTR was achieved significantly more often (p <0.010) using 5-ALA&iMRI (100%) compared to iMRI alone(82%). Mean EoR was significantly(p<0.004) higher in 5-ALA&iMRI-group(99.7%) than in iMRI-alone-group(97.4%) Rate of complications did not differ significantly between groups(21% iMRI-group,27%5-ALA&iMRI-group,p<0.518). nPND were found in 6% in both groups. Median PFS (6mo resp.;p<0.309) and median OS(iMRI:17mo;5-ALA&iMRI-group:18mo;p<0.708)) were not significantly different between both groups.ConclusionWe found a significant increase of EoR when combining 5-ALA&iMRI compared to use of iMRI alone. Maximizing EoR did not lead to an increase of complications or neurological deficits if used with neurophysiological monitoring in eloquent lesions. No final conclusion can be drawn whether a further increase of EoR benefits patient’s progression free survival and overall survival.

A Novel Comprehensive Clinical Stratification Model to Refine Prognosis of Glioblastoma Patients Undergoing Surgical Resection

“…Age, performance status, extent of surgical resection and MGMT methylation status are well known prognostic factors for GBM patients [4,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][39][40][41][42][43][44]. Nevertheless, the high degree of clinical/molecular heterogeneity found among GBM patients do not generally allow us to correctly classify GBM patients with the use of a single predictor or a few predictors.…”

“…To classify GBM cases according to this heterogeneity, different prognostic factors have been suggested for GBM, including age, performance status, specific molecular markers [e.g., MGMT methylation (O 6 -methylguanine-DNA methyl-transferase), mutation of IDH1, IDH2(isocitrate dehydrogenase) or TERT (telomerase reverse transcriptase), 1p19q codeletion, overexpression of EGFR (epidermal growth factor receptor)], the size of necrosis and the extent of resection (EOR) [15][16][17][18][19][20][21][22]. The role of EOR in improving survival in patients with GBM has widely been demonstrated, with more extensive resections providing added advantages [8,9,16,18,19,[23][24][25][26][27][28][29][30][31][32][33].…”

Automatic estimation of extent of resection and residual tumor volume of patients with glioblastoma

“…10,11,25 This has likewise motivated the use of intraoperative 5-aminolevulinic acid fluorescence and electrophysiological mapping and/or intraoperative MRI-assisted surgery in many neurosurgical units in order to reach most radical resections. 8,9,33,35,38 The volumetric measurement of EOR and RTV can be obtained via the manual segmentation of the CET and the postoperative residual, respectively. Kubben et al 23 studied the intrarater and interrater variability of EOR and RTV measurements in 8 patients across 3 different expert raters.…”

Accuracy of High-Field Intraoperative MRI in the Detectability of Residual Tumor in Glioma Grade IV Resections

“…A crucial improvement in glioma resection technique was achieved with fluorescence-guided glioma resection [8]. Since this decade, intraoperative MRI has become an additional technical procedure for intraoperative resection control in glioma surgery [2,15,16]. Eyüpoglu et al used high-field (1.5 T) ioMRI and ALA-guided resection and could show that the extent of resection increases from 84 % to 99 % with the additional usage of ioMRI.…”

“…In a controlled randomized study with a low-field system, Senft et al [16] detected 96 % gross tumor resection in the patient group who were investigated by ioMRI, versus 68 % gross total resection in the control group. Combining the concept of fluorescence-guided tissue resection and ioMRI, Coburger et al found a higher extent of resection with fluorescence-guided resection and ioMRI (100 %) in comparison to ioMRI alone (82 %) [2]. Gessler et al found that ioMRI und fluorescence guidance were inconsistent in 47 % of patients being resected under surveillance with ioMRI in the first line and fluorescence-guided resection after ALA administration in the second line [17].…”